title: Ovariectomized OVA-sensitized mice display increased frequency of CD4(+)Foxp3(+) T regulatory cells in the periphery.
abstract: It is well established that female sex hormones have a pivotal role in inflammation. For instance, our group has previously reported that estradiol has proinflammatory actions during allergic lung response in animal models. Based on these findings, we have decided to further investigate whether T regulatory cells are affected by female sex hormones absence after ovariectomy. We evaluated by flow cytometry the frequencies of CD4(+)Foxp3(+) T regulatory cells (Tregs) in central and peripheral lymphoid organs, such as the thymus, spleen and lymph nodes. Moreover, we have also used the murine model of allergic lung inflammation a to evaluate how female sex hormones would affect the immune response in vivo. To address that, ovariectomized or sham operated female Balb/c mice were sensitized or not with ovalbumin 7 and 14 days later and subsequently challenged twice by aerosolized ovalbumin on day 21. Besides the frequency of CD4(+)Foxp3(+) T regulatory cells, we also measured the cytokines IL-4, IL-5, IL-10, IL-13 and IL-17 in the bronchoalveolar lavage from lungs of ovalbumine challenged groups. Our results demonstrate that the absence of female sex hormones after ovariectomy is able to increase the frequency of Tregs in the periphery. As we did not observe differences in the thymus-derived natural occurring Tregs, our data may indicate expansion or conversion of peripheral adaptive Tregs. In accordance with Treg suppressive activity, ovariectomized and ovalbumine-sensitized and challenged animals had significantly reduced lung inflammation. This was observed after cytokine analysis of lung explants showing significant reduction of pro-inflammatory cytokines, such as IL-4, IL-5, IL-13 and IL-17, associated to increased amount of IL-10. In summary, our data clearly demonstrates that OVA sensitization 7 days after ovariectomy culminates in reduced lung inflammation, which may be directly correlated with the expansion of Tregs in the periphery and further higher IL-10 secretion in the lungs.
authors.affiliation: Programa de Pós-graduação em Biofotônica Aplicada às Ciências da Saúde, Universidade Nove de Julho - UNINOVE, São Paulo, SP, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ligeiro de Oliveira
authors.forename: Jean Pierre Schatzmann
authors.initials: JP
authors.lastname: Peron
authors.forename: Adriana Lino
authors.initials: AL
authors.lastname: Santos Franco
authors.forename: Beatriz Acceturi
authors.initials: BA
authors.lastname: Golega
authors.forename: Rodolfo Paula
authors.initials: RP
authors.lastname: Vieira
authors.forename: Olga Célia Martinez
authors.initials: OC
authors.lastname: Ibanez
authors.forename: Orlando Garcia
authors.initials: OG
authors.lastname: Ribeiro
authors.forename: Wafa Hanna Koury
authors.initials: WH
authors.lastname: Cabrera
authors.forename: Marcelo
authors.initials: M
authors.lastname: De Franco
authors.forename: Ricardo Martins
authors.initials: RM
authors.lastname: Oliveira-Filho
authors.forename: Luiz Vicente
authors.initials: LV
authors.lastname: Rizzo
authors.forename: Bernardo Boris
authors.initials: BB
authors.lastname: Vargaftig
authors.forename: Wothan Tavares
authors.initials: WT
authors.lastname: de Lima
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D015704:CD4 Antigens / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006967:Hypersensitivity / Q000276:immunology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage*; D010052:Ovariectomy; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012739:Gonadal Steroid Hormones; D010047:Ovalbumin